Enantioselective Access to 3,3’-Disubstituted Oxindole-Derivatives by N-heterocyclic Carbene Catalysts

Abstract

An effectively enantioselective and regioselective N-heterocyclic carbene-catalyzed oxidative spiroannulation of isatin-derived enals with 2,4-dioxoesters to directly synthesis of spirooxindole δ-lactones was realized. Subsequently, upon treatment with methanol under reflux, spirooxindole δ-lactones were effectively converted into acyclic 3,3’-disubstituted oxindole-derivatives bearing all-carbon quaternary center. This work provides a practical approach for the in-situ formation of single enantioenriched spirooxindole δ-lactones and acyclic 3,3’-disubstituted oxindole-derivatives under mild reaction conditions. This approach was qualified with broad substrate scope, achieving moderate to excellent yield and enantioselectivity. In addition, scale-up experiments and the synthetic transformations of spirooxindole δ-lactones and acyclic 3,3’-disubstituted oxindole-derivatives further highlighted the synthetic utility.